In this proposal, the applicant will investigate the role of the C-EBP-alpha transcription factor in the development of myeloid cells. It is proposed that this factor plays a key role in the differentiation of such cells from multipotential progenitors. Another transcription factor, PU.1, is an important regulator of myeloid development and, together with C-EBP-alpha, is believed to regulate the promoters for a number of important genes essential for myeloid differentiation. The specific aims are to delineate the role of C-EBP- alpha in myeloid development as well as to define its interaction with PU.1. Thus, the applicant will determine the mechanisms by which C-EBP factors regulate the expression of genes important for myeloid development with particular emphasis on the interaction between C-EBP- alpha and PU.1. He will also determine the effects on targeted disruption of the murine C-EBP-alpha gene on myeloid development in mice and in embryonic stem cells. These studies will be important towards furthering our understanding of hematopoietic lineage development.